Understanding Ultra-Processed Food Intake and Risk of Lupus

Systemic lupus erythematosus has known pathogenesis that includes a combination of inherited genetic predisposition as well as environmental and lifestyle factors. While some environmental triggers have been identified to date - including cigarette smoking, oral contraceptive use, and alcohol – the potential role of diet in development of SLE is not entirely clear. Past cohort studies have not demonstrated strong associations of SLE risk and dietary patterns; however, these studies also did not explore the role of ultraprocessed foods.

Ultraprocessed foods (UPFs) are ready-to-heat/eat formulations of processed food substances and additives that result from high levels of processing with stabilizers, emulsifiers, and other non-nutritional additives. UPFs include food items such as chips, soda, and donuts; a high consumption of UPFs is linked to obesity and other chronic diseases like cardiovascular disease, type 2 diabetes, and increased mortality. This study by Rossato et al examined whether consumption of UPFs was associated with increased incidence of SLE among women in the prospective Nurses’ Health Study (NHS) cohorts (1).

This study was an observational study of prospective cohort of US registered nurses, the NHSI and NHSII which enrolled over 121,000 and 116,000 women respectively in their 20s to 50s from 1976 (NHS) and 1989 (NHSII). Participants completed self-reported dietary intake via the validated semiquantitative food frequency questionnaire (SQFFQ), which assessed dietary intake every 4 years including frequency of consumption of UPF.

The UPF intake was calculated including servings of UPF/day, g, or mL of UPF intake per day, and the percentage of total food intake that were UPF. Covariates were self-reported on mailed questionnaires administered every two years. Incidental diagnoses of SLE that were self-reported were confirmed by rheumatologists.

The authors calculated the cumulative average of UPF intake, which were ranked in tertiles to compare highest to lowest tertile group, which was used as the reference group. Time-varying Cox regression models were used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals for patients with incident SLE. Models were adjusted for age, race, age at menarche, body mass index (BMI), menopausal status, total caloric intake and alcohol intake, smoking, oral contraceptive use, household income, and postmenopausal hormone use.

Risk of SLE with and without anti-double stranded DNA (dsDNA) antibody at time of diagnosis was assessed. Stratified analysis was obtained to investigate potential effect modification by BMI, stratifying participants by BMI, adjusting for total caloric intake.

The study enrolled approximately 99,000 women from NHSI and nearly 106,000 women in NHSII. The average age was 50 and 36 in NHSI and NHSII respectively; over 90% of participants identified as White race. There were 212 patients with incident SLE identified. In the multivariable pooled analyses, the risk for developing SLE was higher in the third versus first UPF tertile (servings/day) with HR 1.56 (P = .03).

The results were stronger for dsDNA positive SLE (servings/day) with HR 2.05 (P = .01). Thus, higher cumulative UPF intake was associated with an over 50% increased risk for developing SLE. Additional analyses showed both artificially sweetened and sugar-sweetened beverages were most strongly associated with the risk of developing SLE. Limitations of the study include majority of white female nurses within the United States with relatively high baseline age (especially NHS around 50 years old, after peak incidence of SLE); future studies should be replicated in more diverse and younger cohorts.

This study provides novel data demonstrating an association between higher daily consumption of ultraprocessed foods and higher incidence of developing lupus. UPFs are known to increase systemic inflammation. Potential mechanisms of how UPFs cause the increased risk of SLE include deleterious epigentic changes or changes to gut epithelia and the microbiome. Given UPF intake represents over half of total caloric intake in the average US diet, it is critical to work on educating the public on reducing this for overall health benefits, with a potential influence in reducing the rates of incident SLE and other chronic diseases.

References:

Rossato S, Oakes EG, Barbhaiya M et al. Ultraprocessed Food Intake and Risk of Systemic Lupus Erythematosus Among Women Observed in the Nurses' Health Study Cohorts. Arthritis care & research, June 2024. 10.1002/acr.25395.